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Senior Citizen Health & Medicine
Prostate Cancer Cells Killed by RNA-Based Drug
Duke University files for patent on experimental technology
August 10, 2006 - Acting as a genetic Trojan horse,
an experimental RNA-based drug -- the first of its kind -- tricks its
way into prostate cancer cells and then springs into action to destroy
them, while leaving normal cells unharmed. Prostate cancer is most
common in older men, with 70 being the average age of diagnosis.
The drug, developed at Duke University Medical
Center, uses one type of genetic material, called targeting RNA, to
enter cancer cells, and another type, called silencing RNA, to stop the
expression of a protein that keeps the cells alive.
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In tests in mice with prostate cancer, the drug
shrank the size of their tumors by half, while the tumors in control
mice that did not receive the drug continued to grow, said study
co-author Bruce Sullenger, Ph.D., director of Duke's Translational
Research Institute and chief of the Division of Experimental Surgery.
The mice showed no side effects from the treatment,
Sullenger said.
"This study represents the first step in creating
an RNA-based drug for cancer," said lead author James McNamara, Ph.D. a
postdoctoral fellow in experimental surgery. "It provides a 'proof of
principle' that an entirely RNA-based drug can work with minimal side
effects, and it shows it is possible to overcome many of the obstacles
that have hampered the development of RNA-based drugs."
The study is reported in the August 2006 issue of
Nature Biotechnology, which is now available online. The research was
funded by the National Institutes of Health.
Duke has filed a provisional patent application on
the technology, according to the researchers.
"Scientists have made numerous attempts to
transform silencing RNAs into natural anticancer agents, but such
development has been challenging," said Paloma Giangrande, Ph.D.,
co-leader of the study and an assistant research professor in
experimental surgery.
Scientists have encountered major obstacles when
trying to deliver silencing RNAs to tumors, Giangrande said. Previous
RNA-based drugs have been nonspecific, targeting all cells in the body
and not just cancer cells. As a result, they have caused unwanted side
effects.
The Duke team set out to produce a drug that would
target only cancer cells. To accomplish this goal, the researchers
designed a drug that combines two RNA "modules" that work in stages. One
module contains targeting RNA, which attaches to a protein, PMSA, found
only on the surface of prostate cancer cells. When that module binds to
a cancer cell, the cell reacts by engulfing the entire drug molecule.
With the drug now inside the cancer cell, the
second module, which contains silencing RNA, launches its effect. The
silencing RNA seeks out and binds to the RNA for a specific
cancer-causing protein, called PLK1, and tags it for destruction. This
eventually leads to the death of the cancer cell.
The researchers first tested the drug in culture
dishes containing cancer cells. They found that the drug effectively
bound to prostate cancer cells, entered them and shut off production of
the target protein, PLK1.
The researchers then moved into mouse experiments.
They injected the drug directly into the mice's prostate tumors,
administering one injection every two days, for a total of 10 injections
over 20 days. By the end of the study, the tumors in the 10 treated mice
had shrunk two-fold in volume, while the tumors in the 10 control
animals had more than tripled in size.
"The animals themselves showed no signs of side
effects," Giangrande said.
The scientists caution that much work remains to
move the experimental drug into clinical use in humans. Among the next
steps, Sullenger said, is to demonstrate conclusively that the drug can
be delivered into the blood stream and still reach the tumor target
without being destroyed by the body or causing adverse side effects.
Other Duke researchers involved in the study
include Eran Andrechek, Yong Wang, Kristi Viles, Rachel Rempel and Eli
Gilboa.
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